The tissue destruction of periodontitis may be a direct consequence of interactions between components of the inflammatory exudate and external stimuli. The human mononuclear phagocyte (HMP), a prominent component of inflammatory exudates, has been implicated in the production of several substances that can mediate or modulate inflammatory processes. Of principal interest in this proposal is HMP produced prostaglandin, a potent modulator of inflammatory processes. HMP are the main source of leukocyte prostaglandin. The primary objective of this proposal is to study in detail the capacity of biologically active fragments of the 3rd component, C3band C3bi, to enhance the release of prostaglandin by HMP in vitro. We have demonstrated that soluble immune complexes, C3b and C3bi enhance prostaglandin release by HMP. The nature of the stimulus-secretion coupling as regards the metabolic events which link the binding of C3b to HMP receptors to the synthesis and release of prostaglandin and other metabolites or arachidonic acid will be studied. Of particular interest are 1) the interrelationships between the stimuli which induce release, 2) the C3b induced alterations in cellular phospholipids which lead to release, 3) the stability of secretory phenotype, 4) the effects of exogenous arachidonic acid, 5) the effects of lymphocytes and 6) spectrum of arachidonic acid metabolites released. Insoluble and soluble immune complexes and purified C3b and C3bi will be used to stimulate HMP purified by counterflow centrifugation and cultured under defined (serum-free) conditions. This highly refined system is ideal for the quantitative and qualitative evaluation of HMP arachidonic acid metabolism. The data generated by these experiments will further elucidate the role of complement in the control of the release of prostaglandins and other metabolites of arachidonic acid. Hence further insight into the role of complement and cells of the monocyte/macrophage series in the control of inflammation and the pathogenesis of inflammatory diseases will be gained.